Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison's disease.

Among bone turnover markers evaluated, only PINP levels were altered in Addison's disease patients on hydrocortisone replacement.

• 80 patients with AD were assessed (22 males, 25 pre- and 33 postmenopausal females)
• All patients were on hydrocortisone substitution for ≥3 years
• BTMs assessed included osteocalcin, PINP, CTX, sclerostin, DKK-1 protein, and alkaline phosphatase (ALP)
• CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remained within reference ranges

BMD Z-scores remained negative across patient groups except for femoral neck in males.

• Densitometry covered lumbar spine (LS) and femoral neck (FN) using dual-energy X-ray absorptiometry
• Osteopenia in LS was found in 45.5% of males, 24% of premenopausal females, and 42.4% of postmenopausal females
• Osteoporosis was found in 9.0% of males, 4.0% of premenopausal females, and 21.1% of postmenopausal females
• Femoral neck BMD Z-scores in males were the exception to the pattern of negative Z-scores

Lumbar spine BMD correlated positively with body mass and serum DHEA-S.

• Positive correlation with body mass: p = 0.0001
• Positive correlation with serum DHEA-S: p = 9.899 × 10⁻⁶

Lumbar spine BMD showed negative correlations with hydrocortisone dose, cumulative HC dose, age, disease duration, ALP activity, and CTX level.

• Negative correlation with HC dose/day/kg: p = 0.0320
• Negative correlation with cumulative HC dose: p = 0.0030
• Negative correlation with patient's age: p = 1.038 × 10⁻⁵
• Negative correlation with disease duration: p = 0.0004
• Negative correlation with ALP activity: p = 0.0041
• Negative correlation with CTX level: p = 0.0105

Only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of lumbar spine BMD.

• Multivariate analysis identified five independent predictors of LS BMD
• Hydrocortisone dose variables did not remain independent predictors after multivariate analysis
• DHEA-S and disease duration were not independent predictors after adjustment
• ALP activity, serum CTX, and sclerostin were highlighted as particularly notable independent predictors that might be monitored during GC substitution

Standard hydrocortisone substitution does not considerably accelerate BMD loss in Addison's disease patients.

• Study population included 80 AD patients on long-term HC substitution (≥3 years)
• BTMs largely remained within reference ranges despite long-term GC replacement
• The authors concluded bone effects of substitution doses in AD remain equivocal
• The finding contrasts with known risks of osteoporosis in patients receiving pharmacological glucocorticoid doses